The intervention of endoperoxides in the biogenesis of prostaglandins, the complete lack of organochemical preparative methods for the endoperoxide skeleton, the potent biological activity of these labile intermediates and the biomechanistic ambiguities of lipoxygenase action, have precipitated our interest in this interdisciplinary field. Our Prostaglandin Endoperoxide research entails the synthesis of these cyclic peroxides via new routes based on 1) designing substrates with oxygenation-specific sites, b) developing site-specific oxygenation agents, and c) generating oxidative cyclization methods. In the synthetic approaches cognizance is made of the thermal lability of the prostanoid intermediates by employing subambient reaction, isolation and purification techniques. We shall utilize hydrogen peroxide, singlet oxygen, superoxide, ketonoxide, hypofluorite and sulfoxylate cyclizations. Model studies for the oxygenative bicyclization step in the biogenesis of the prostanoid endoperoxide from arachidonic acid shall be undertaken in order to elucidate the bio-mechanism of lipoxygenase action. Especially promising appears the utilization of the mechanistically bifunctional superoxide radical anion, whose negative charge lends it nucleophilic power and the unpaired electron free radical activity. Free radical initiated and cationic bicyclization of unsaturated hydroperoxides and direct singlet oxygenation of 1,5-dienes shall be explored. It is expected that through this research we should also uncover useful drugs for the diagnosis, therapy, and prevention of disorders connected with the diverse physiological functions of the respiratory, cardiovascular, reproductive, gastric, renal and nervous systems, all monitored by prostaglandins. BIBLIOGRAPHIC REFERENCES: W. Adam and O. Cueto (1977), "A Convenient Preparation of Aromatic alpha-Hydroperoxy Acids via Oxygenation of alpha-Lithio Enolates Prepared by Direct alpha-Lithiation of Arylacetic Acids", J. Org. Chem., 42, 38-40. W. Adam and R.S.C. Tsai (1977), "Electron Impact Behavior of beta-Peroxylactones", J. Org. Chem., approximately 42, 537-541.